Neurosurgical Research Institute, The First Affiliated Hospital of Guangdong Pharmaceutics University, Guangzhou, Guangdong, China.
Guangdong Province Key Laboratory of Brain Function and Disease, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
Mol Carcinog. 2018 Sep;57(9):1181-1190. doi: 10.1002/mc.22834. Epub 2018 May 18.
Gliomas are common, aggressive central nervous system tumors with poor overall survival rates. Despite improvements in neurosurgery, chemotherapy, and radiotherapy, the outcomes of patients with malignant gliomas remain poor. Therefore, increased knowledge of the molecular mechanisms that regulate glioma progression is crucial to identify novel therapeutic targets. Here, we reported that SHCBP1, a member of Src homolog and collagen homolog (Shc) family, was significantly overexpressed in glioma tissues and glioma cell lines compared to the corresponding normal tissues and cells. Ectopic overexpression of SHCBP1 promoted glioma cell migration and invasion, whereas knockdown of endogenous SHCBP1 had the opposite effects. Importantly, we demonstrated that SHCBP1 promoted aggressiveness in gliomas by activating the NF-κB signaling pathway. Collectively, our study indicates that SHCBP1 plays a pivotal role to promote progression in gliomas and targeting the oncogenic effects of SHCBP1 may provide a clinical strategy to treat gliomas.
神经胶质瘤是常见的侵袭性中枢神经系统肿瘤,总体生存率较差。尽管神经外科、化疗和放疗有所改善,但恶性神经胶质瘤患者的预后仍然较差。因此,增加对调节神经胶质瘤进展的分子机制的了解对于确定新的治疗靶点至关重要。在这里,我们报道了Src 同源和胶原同源 (Shc) 家族的成员 SHCBP1 在神经胶质瘤组织和神经胶质瘤细胞系中明显过表达,与相应的正常组织和细胞相比。SHCBP1 的异位过表达促进了神经胶质瘤细胞的迁移和侵袭,而内源性 SHCBP1 的敲低则产生了相反的效果。重要的是,我们证明 SHCBP1 通过激活 NF-κB 信号通路促进神经胶质瘤的侵袭性。总之,我们的研究表明 SHCBP1 在促进神经胶质瘤进展中起关键作用,针对 SHCBP1 的致癌作用可能为治疗神经胶质瘤提供一种临床策略。